Chemistry on the microscale, involving the reaction and subsequent analysis of reagents or analytes in microliter volumes or smaller, is an increasingly important aspect of the study and/or development of substances in the pharmaceutical and other industries. In certain instances, the reagents or analytes are scarce or otherwise not easily obtainable. In other instances, such as is prevalent in biopharmaceutical research, the analytical objectives sought call for the extraction of a vast library of information from a correspondingly vast number of assays. In either instance—whether by necessity (as in the former) or as a practical matter (as in the latter)—microscale chemistry provides apparent and distinct advantages.
Often in biopharmaceutical research, an assay, as part of its protocol, requires a fluid filtration step, for example, to either purify or isolate a particular biochemical target. For conducting several of such assays contemporaneously, so-called “multiwell plates” have become the tool of choice. These are now mass produced and obtainable easily from several commercial venues (e.g., Millipore Corporation of Billerica, Mass.). They are generally fast, easy to use, comparatively inexpensive, and amenable to automated robotic processes.
Multiwell plates are frequently used, for example, to incubate microcultures or to separate biological or biochemical material followed by further processing to harvest the material. Each well in a typical multiwell plate is provided with separation material so that, upon application of suitable force (e.g., a vacuum) to one side of the plate, fluid in each well is expressed through the filter, leaving solids (e.g., bacteria, precipitated protein, and the like) entrapped therein. The separation material can also act as a membrane such that the predetermined target is selectively bonded or otherwise retained. The retained target can thereafter be harvested by means of a further solvent. The liquid expressed from the individual wells through the separation material can be collected in a common collecting vessel (e.g., in instances wherein the liquid is not needed for further processing), or alternatively, in individual collecting containers.
Existing multiwell plates are often manufactured in 6-well, 24-well, 96-well, 384-well, and 1536-well formats, each well typically having a predetermined maximum volume capacity ranging between approximately 1 microliter to approximately 5 milliliters. Typically, each well in a multiwell plate is provided with a corresponding underdrain downstream of the separation material. The underdrain—often provided with a spout—essentially controls or otherwise affects the nature of and manner in which fluid is discharged out each well.
Multiwell plates having underdrains with spouts are disclosed, for example, in U.S. Pat. No. 4,902,481, issued to P. Clark et aL. on Feb. 20, 1990; U.S. Pat. No. 5,264,184, issued to J. E. Aysta et al. on Nov. 23, 1993; U.S. Pat. No. 5,464,541, issued to J. E. Aysta et al. on Nov. 7, 1995; U.S. Pat. No. 5,108,704, issued to W. F. Bowers et al. on Apr. 28, 1992; U.S. patent Application. Pub. No. 2002/0,195,386, filed by S. G. Young et al. on Jun. 25, 2002; U.S. Pat. No. 4,948,564, issued to D. Root et al. on Aug. 14, 1990; U.S. patent application Pub. No. 2002/0,155,034, filed by C. A. Perman on Jun. 11, 2002; U.S. Pat. No. 6,338,802, issued to K. S. Bodner et al on Jan. 15, 2002; U.S. Pat. No. 6,159,368, issued to S. E. Moring etal. on Dec. 12, 2000; U.S. Pat. No. 5,141,719, issued to G. C. Fernwood et al. on Aug. 25, 1992; U.S. Pat. No. 6,391,241, issued to R. A. Cote et al. on May 21, 2002; U.S. patent application Pub. No. 2002/0,104,795, filed by R. A. Cote et al. on Mar. 28, 2002; U.S. Pat. No. 6,419,827, issued to D. R. Sandell et aL. on Jul. 16, 2002; PCT International Patent Application Pub. No. WO 02/096563, filed by J. Kane et al. on May 29, 2002; PCT International Patent Application Pub. No. WO 01/51206, filed by T. Vaaben et al. on May 8, 2000; and PCT International Patent Application Pub. No. WO 01/45,844, filed by K. A. Moll on Dec. 21, 2000.
While these and other multiwell plates are still widely used, need is felt for both structural and functional improvements thereto. Areas of particular interest include, but are not limited to, the control of so-called “pendant drop formation”, cross-talk between wells, and robotic automation.
In particular, as known by those skilled in the art, fluid is often expressed (intentionally or not) through a multiwell plate in drops. The nature of drop formation will affect the conduct of robotic automation, for example, the speed, precision, and sensitivity thereof. Undesirable drop formation and dripping can lead, for example, to sample loss, leakage, splattering, cross contamination (i.e., cross talk), exposure to hazardous media, downstream equipment contamination, and the like. Loss of information, diagnostic failures, and other (potentially catastrophic) inaccuracies can result. These and other like issues are particularly pronounced in protocols that involve comparatively long storage and/or incubation periods.